Shaping the synapse through neuronal activity-regulated miRNAs.

Abstract

The brain's ability to adapt and support learning relies on experience-dependent synaptic plasticity, where connections between neurons are strengthened or weakened in response to activity. Recent research in mammalian systems reveals microRNAs (miRNAs) as crucial regulators of this process, offering a new perspective on how neurons achieve timely, localized control of protein synthesis. Neuronal activity influences every stage of the miRNA life cycle, from transcription to transport, maturation, and decay. Transcriptional regulation enables neuron-wide structural adaptations, while synapse-specific transport and maturation ensure localized protein synthesis. Though incompletely understood, activity-regulated miRNA decay allows for reversible modulation of gene expression. These discoveries highlight miRNAs as an essential layer of regulation, bridging neuronal activity with molecular changes that support learning and memory.